Dr. Al Ghouleh is an Associate Professor of Medicine and Principal Investigator in the Cardiovascular Research Center Brown University Health Cardiovascular Institute and at The Warren Alpert Medical School of Brown University. Dr. Al Ghouleh's research is conducted at the Vascular Research Laboratory located at the Providence VA Medical Center.
Dr. Al Ghouleh completed his training in vascular, redox, and free radical biology. He received his PhD from McGill University in Montreal, Canada, studying the role of NADPH oxidase (Nox) in vascular endothelial dysfunction during sepsis, followed by postdoctoral training at the University of Pittsburgh studying vascular dysfunction and feed-forward ROS and Nox signaling in systemic and pulmonary hypertension.
The Al Ghouleh lab is focused on elucidating the molecular mechanisms underlying vascular remodeling and right heart dysfunction in pulmonary hypertension with a focus on the role of microbiome-derived metabolites.
| Prisco SZ, Oliveira SD, Weir EK, Thenappan T, Al Ghouleh I. "Gut Microbiome in Pulmonary Arterial Hypertension-An Emerging Frontier." Infectious disease reports, vol. 17, no. 3, 2025. |
| Goossen CJ, Kufner A, Dustin CM, Al Ghouleh I, Yuan S, Straub AC, Sembrat J, Baust JJ, Gomez D, Kračun D, Pagano PJ. "Redox regulation of lung endothelial PERK, unfolded protein response (UPR) and proliferation via NOX1: Targeted inhibition as a potential therapy for PAH." Redox biology, vol. 82, 2025, pp. 103554. |
| Jose A, Yogeswaran A, Fuenderich M, Kiely D, Sweatt AJ, Zamanian RT, Hassoun PM, Mouawad A, Balasubramanian A, Wilkins M, Lawrie A, Howard L, Sahay S, Olschewski H, Kovacs G, Saleh K, Sabbour H, Eichstaedt CA, Grünig E, Giannakoulas G, Arvanitaki A, Sirenko Y, Torbas O, Cajigas H, Frantz R, Scelsi L, Ghio S, Majeed RW, Wilhelm J, Ghofrani HA, Grimminger F, Tello K, Elwing J, Seeger W, PVRI‐GoDeep‐Consortium. "Survival Outcomes and Impact of Targeted PAH Therapy in Portopulmonary Hypertension in the PVRI GoDeep Meta-Registry." Pulmonary Circulation, vol. 15, no. 3, 2025, pp. e70121. |
| Yogeswaran A, Gall H, Fünderich M, Wilkins MR, Howard L, Kiely DG, Lawrie A, Hassoun PM, Sirenklo Y, Torbas O, Sweatt AJ, Zamanian RT, Williams PG, Frauendorf M, Arvanitaki A, Giannakoulas G, Saleh K, Sabbour H, Cajigas HR, Frantz R, Al Ghouleh I, Chan SY, Brittain E, Annis JS, Pepe A, Ghio S, Orfanos S, Anthi A, Majeed RW, Wilhelm J, Ghofrani HA, Richter MJ, Grimminger F, Sahay S, Tello K, Seeger W, Pulmonary Vascular Research Institute GoDeep Consortium. "Comparison of Contemporary Risk Scores in All Groups of Pulmonary Hypertension: A Pulmonary Vascular Research Institute GoDeep Meta-Registry Analysis." Chest, vol. 166, no. 3, 2024, pp. 585-603. |
| Al Ghouleh I, Pulgarin Rocha A, Goncharova EA. "New Kid on the Block: GLI1+ Cells and Pulmonary Arterioles Neomuscularization." Circulation research, vol. 134, no. 11, 2024, pp. 1402-1404. |
| Rajaratnam A, El-Swais A, McTiernan C, Thoma FW, Baghal MO, Raffensperger K, Chang CH, Hickey GW, Shah FA, Al Ghouleh I. "Persistence of pulmonary hypertension in patients undergoing ventricular assist devices and orthotopic heart transplantation." Pulmonary Circulation, vol. 13, no. 4, 2023, pp. e12296. |
| Majeed RW, Wilkins MR, Howard L, Hassoun PM, Anthi A, Cajigas HR, Cannon J, Chan SY, Damonte V, Elwing J, Förster K, Frantz R, Ghio S, Al Ghouleh I, Hilgendorff A, Jose A, Juaneda E, Kiely DG, Lawrie A, Orfanos SE, Pepe A, Pepke-Zaba J, Sirenko Y, Swett AJ, Torbas O, Zamanian RT, Marquardt K, Michel-Backofen A, Antoine T, Wilhelm J, Barwick S, Krieb P, Fuenderich M, Fischer P, Gall H, Ghofrani HA, Grimminger F, Tello K, Richter MJ, Seeger W. "Pulmonary Vascular Research Institute GoDeep: A meta-registry merging deep phenotyping datafrom international PH reference centers." Pulmonary Circulation, vol. 12, no. 3, 2022, pp. e12123. |
| Vanderpool RR, Gorelova A, Ma Y, Alhamaydeh M, Baust J, Shiva S, Tofovic SP, Hu J, Nouraie SM, Gladwin MT, Sharifi-Sanjani M, Al Ghouleh I. "Reversal of Right Ventricular Hypertrophy and Dysfunction by Prostacyclin in a Rat Model of Severe Pulmonary Arterial Hypertension." International Journal of Molecular Sciences, vol. 23, no. 10, 2022. |
| DeVallance ER, Dustin CM, de Jesus DS, Ghouleh IA, Sembrat JC, Cifuentes-Pagano E, Pagano PJ. "Specificity Protein 1-Mediated Promotion of CXCL12 Advances Endothelial Cell Metabolism and Proliferation in Pulmonary Hypertension." Antioxidants, vol. 12, no. 1, 2022. |
| Negi V, Yang J, Speyer G, Pulgarin A, Handen A, Zhao J, Tai YY, Tang Y, Culley MK, Yu Q, Forsythe P, Gorelova A, Watson AM, Al Aaraj Y, Satoh T, Sharifi-Sanjani M, Rajaratnam A, Sembrat J, Provencher S, Yin X, Vargas SO, Rojas M, Bonnet S, Torrino S, Wagner BK, Schreiber SL, Dai M, Bertero T, Al Ghouleh I, Kim S, Chan SY. "Computational repurposing of therapeutic small molecules from cancer to pulmonary hypertension." Science Advances, vol. 7, no. 43, 2021, pp. eabh3794. |
| Gorelova A, Berman M, Al Ghouleh I. "Endothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension." Antioxidants & redox signaling, vol. 34, no. 12, 2021, pp. 891-914. |
| Potus F, Frump AL, Umar S, R Vanderpool R, Al Ghouleh I, Lai YC. "Recent advancements in pulmonary arterial hypertension and right heart failure research: overview of selected abstracts from ATS2020 and emerging COVID-19 research." Pulmonary Circulation, vol. 11, no. 3, 2021, pp. 20458940211037274. |
| Sharifi-Sanjani M, Berman M, Goncharov D, Alhamaydeh M, Avolio TG, Baust J, Chang B, Kobir A, Ross M, St Croix C, Nouraie SM, McTiernan CF, Moravec CS, Goncharova E, Al Ghouleh I. "Yes-Associated Protein (Yap) Is Up-Regulated in Heart Failure and Promotes Cardiac Fibroblast Proliferation." International Journal of Molecular Sciences, vol. 22, no. 11, 2021. |
| Song GJ, Gupta DP, Rahman MH, Park HT, Al Ghouleh I, Bisello A, Lee MG, Park JY, Park HH, Jun JH, Chung KW, Choi BO, Suk K. "Loss-of-function of EBP50 is a new cause of hereditary peripheral neuropathy: EBP50 functions in peripheral nerve system." Glia, vol. 68, no. 9, 2020, pp. 1794-1809. |
| Rafikova O, Al Ghouleh I, Rafikov R. "Focus on Early Events: Pathogenesis of Pulmonary Arterial Hypertension Development." Antioxidants & redox signaling, vol. 31, no. 13, 2019, pp. 933-953. |
| Csányi G, Feck DM, Ghoshal P, Singla B, Lin H, Nagarajan S, Meijles DN, Al Ghouleh I, Cantu-Medellin N, Kelley EE, Mateuszuk L, Isenberg JS, Watkins S, Pagano PJ. "CD47 and Nox1 Mediate Dynamic Fluid-Phase Macropinocytosis of Native LDL." Antioxidants & redox signaling, vol. 26, no. 16, 2017, pp. 886-901. |
| Ghouleh IA, Sahoo S, Meijles DN, Amaral JH, de Jesus DS, Sembrat J, Rojas M, Goncharov DA, Goncharova EA, Pagano PJ. "Endothelial Nox1 oxidase assembly in human pulmonary arterial hypertension; driver of Gremlin1-mediated proliferation." Clin. Sci., vol. 131, no. 15, 2017, pp. 2019-2035. |
| Meijles DN, Sahoo S, Al Ghouleh I, Amaral JH, Bienes-Martinez R, Knupp HE, Attaran S, Sembrat JC, Nouraie SM, Rojas MM, Novelli EM, Gladwin MT, Isenberg JS, Cifuentes-Pagano E, Pagano PJ. "The matricellular protein TSP1 promotes human and mouse endothelial cell senescence through CD47 and Nox1." Science Signaling, vol. 10, no. 501, 2017. |
| Al Ghouleh I, Meijles DN, Mutchler S, Zhang Q, Sahoo S, Gorelova A, Henrich Amaral J, Rodríguez AI, Mamonova T, Song GJ, Bisello A, Friedman PA, Cifuentes-Pagano ME, Pagano PJ. "Binding of EBP50 to Nox organizing subunit p47phox is pivotal to cellular reactive species generation and altered vascular phenotype." Proceedings of the National Academy of Sciences, vol. 113, no. 36, 2016, pp. E5308-17. |
| Sahoo S, Meijles DN, Al Ghouleh I, Tandon M, Cifuentes-Pagano E, Sembrat J, Rojas M, Goncharova E, Pagano PJ. "MEF2C-MYOCD and Leiomodin1 Suppression by miRNA-214 Promotes Smooth Muscle Cell Phenotype Switching in Pulmonary Arterial Hypertension." PLoS ONE, vol. 11, no. 5, 2016, pp. e0153780. |
| Magder S, Parthenis DG, Ghouleh IA. "Preservation of renal blood flow by the antioxidant EUK-134 in LPS-treated pigs." International Journal of Molecular Sciences, vol. 16, no. 4, 2015, pp. 6801-17. |
| Frazziano G, Al Ghouleh I, Baust J, Shiva S, Champion HC, Pagano PJ. "Nox-derived ROS are acutely activated in pressure overload pulmonary hypertension: indications for a seminal role for mitochondrial Nox4." AJP: Heart and Circulatory Physiology, vol. 306, no. 2, 2014, pp. H197-205. |
| Al Ghouleh I, Frazziano G, Rodriguez AI, Csányi G, Maniar S, St Croix CM, Kelley EE, Egaña LA, Song GJ, Bisello A, Lee YJ, Pagano PJ. "Aquaporin 1, Nox1, and Ask1 mediate oxidant-induced smooth muscle cell hypertrophy." Cardiovascular research, vol. 97, no. 1, 2013, pp. 134-42. |
| Cifuentes-Pagano E, Saha J, Csányi G, Ghouleh IA, Sahoo S, Rodríguez A, Wipf P, Pagano PJ, Skoda EM. "Bridged tetrahydroisoquinolines as selective NADPH oxidase 2 (Nox2) inhibitors." MedChemComm, vol. 4, no. 7, 2013, pp. 1085-1092. |
| Al Ghouleh I, Rodríguez A, Pagano PJ, Csányi G. "Proteomic analysis identifies an NADPH oxidase 1 (Nox1)-mediated role for actin-related protein 2/3 complex subunit 2 (ARPC2) in promoting smooth muscle cell migration." International Journal of Molecular Sciences, vol. 14, no. 10, 2013, pp. 20220-35. |
| Al Ghouleh I, Magder S. "NADPH oxidase-derived superoxide destabilizes lipopolysaccharide-induced interleukin 8 mRNA via p38, extracellular signal-regulated kinase mitogen-activated protein kinase, and the destabilizing factor tristetraprolin." Shock, vol. 37, no. 4, 2012, pp. 433-40. |
| Csányi G, Yao M, Rodríguez AI, Al Ghouleh I, Sharifi-Sanjani M, Frazziano G, Huang X, Kelley EE, Isenberg JS, Pagano PJ. "Thrombospondin-1 regulates blood flow via CD47 receptor-mediated activation of NADPH oxidase 1." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 32, no. 12, 2012, pp. 2966-73. |
| Cascino T, Csanyi G, Al Ghouleh I, Montezano AC, Touyz RM, Haurani MJ, Pagano PJ. "Adventitia-derived hydrogen peroxide impairs relaxation of the rat carotid artery via smooth muscle cell p38 mitogen-activated protein kinase." Antioxidants & redox signaling, vol. 15, no. 6, 2011, pp. 1507-15. |
| Al Ghouleh I, Pagano PJ. "Endosomal ClC-3 and Nox1: moving marksmen of redox signaling?." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 31, no. 2, 2011, pp. 240-2. |
| Csányi G, Cifuentes-Pagano E, Al Ghouleh I, Ranayhossaini DJ, Egaña L, Lopes LR, Jackson HM, Kelley EE, Pagano PJ. "Nox2 B-loop peptide, Nox2ds, specifically inhibits the NADPH oxidase Nox2." Free Radical Biology and Medicine, vol. 51, no. 6, 2011, pp. 1116-25. |
| Al Ghouleh I, Khoo NK, Knaus UG, Griendling KK, Touyz RM, Thannickal VJ, Barchowsky A, Nauseef WM, Kelley EE, Bauer PM, Darley-Usmar V, Shiva S, Cifuentes-Pagano E, Freeman BA, Gladwin MT, Pagano PJ. "Oxidases and peroxidases in cardiovascular and lung disease: new concepts in reactive oxygen species signaling." Free Radical Biology and Medicine, vol. 51, no. 7, 2011, pp. 1271-88. |
| Al Ghouleh I, Magder S. "Nicotinamide adenine dinucleotide phosphate (reduced form) oxidase is important for LPS-induced endothelial cell activation." Shock, vol. 29, no. 5, 2008, pp. 553-9. |
Dr. Al Ghouleh’s lab is primarily focused on studying pulmonary hypertension (PH), a devastating disease with no existing curative treatment. There are three main research areas in the lab:
As PH progresses, extensive remodeling occurs in the blood vessels that compose the pulmonary circulation which leads to progressive increases in pulmonary vascular resistance. This in turn causes pressure overload on the right ventricle (RV) of the heart which undergoes remodeling as a result. Initially, RV remodeling is adaptive but eventually becomes maladaptive and leads to RV failure. To date, there is no curative treatment for PH and no therapies exist that can reverse the vascular remodeling in this rapidly progressive disease. Moreover, there are no therapies to target RV remodeling, dysfunction or failure.
One main area of research in the Al Ghouleh lab is defining the mechanisms that underlie right ventricular phenotypic changes in PH through studying the role of the NHE regulatory factor (NHERF) protein family in RV dysfunction and cardiac fibroblast reprogramming. The lab uses in vivo models of PH and RV pressure overload challenge as well as in vitro approaches to delineate the upstream and downstream mechanisms connected to this pathway with a long-term focus on translating mechanistic insights into therapeutic strategies aimed at the RV.
Another area of major focus in the lab is to study the mechanisms of pulmonary vascular endothelial cell reprogramming in PH. The endothelium plays a critical role in the initiation and progression of vascular remodeling, but the underlying mechanisms remain incompletely understood. Emerging research has implicated the process of endothelial-to-mesenchymal transdifferentiation (EndMT) to play a role in the pathogenesis of PH. Preliminary findings from the lab implicated NHERF proteins as an upstream driving force behind EndMT in the pulmonary vasculature. Current research in the lab is focused on fully elucidating this pathway and gaining a deeper understanding of the underlying forces that drive EndMT in PH and how this process contributes to pulmonary vascular remodeling.
Linked to these, an emerging interest in the lab is to gain an understanding of the potential association between PH and changes (and consequences of changes) in the composition of host microbial communities. In recent years, there has been an increasing appreciation of the role of the microbiome in various diseases, including systemic cardiovascular diseases such as atherosclerosis. Recent evidence has also supported an association between the microbiome and PH. The lab is actively engaged in testing this association and uncovering the mechanistic underpinnings of this link. We are interested in dissecting the molecular origins of host-microbiome cross-talk and the role of microbiome-derived metabolites, such as short-chain fatty acids, in endothelial dysfunction and reprogramming in PH.
| Year | Degree | Institution |
|---|---|---|
| 2009 | PhD | McGill University |
| 2001 | BA | McGill University |
| 2000 | BSc | McGill University |
